Bortezomib in Treating Patients With Advanced Myeloproliferative Disorders

Early Phase 1

Completed

• Conditions: Chronic Myeloproliferative Disorders; Leukemia
• Interventions: Drug: PS-341

• Registration Number: NCT00437086
• Lead Sponsor: Mayo Clinic

Brief Summary

RATIONALE: Bortezomib may stop the growth of abnormal cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the abnormal cells.

PURPOSE: This clinical trial is studying the side effects and how well bortezomib works in treating patients with advanced myeloproliferative disorders.

Detailed Description

OBJECTIVES:

Primary

* Determine the efficacy of bortezomib in patients with symptomatic advanced myeloproliferative disorders (i.e., myelofibrosis with myeloid metaplasia, chronic myelomonocytic leukemia, or FIP1LI-PDGFRA-negative mast cell disease).

* Determine the safety of this drug when administered on a modified schedule in these patients.

Secondary

* Determine the effect of this drug on bone marrow cellularity, tryptase-positive mast cells, reticulin fibrosis, osteosclerosis, and angiogenesis in responding patients

OUTLINE: This is a prospective, open-label, pilot, multicenter study. Patients are stratified according to disease (systemic mast cell disease vs chronic myelomonocytic leukemia vs myelofibrosis with myeloid metaplasia).

Patients receive bortezomib IV weekly for 4 weeks. Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a response (complete remission, partial remission, or minimal remission) after 2 courses may receive an additional 6 courses of therapy. Patients who achieve stable disease with acceptable toxicities after 2 courses receive bortezomib IV at a higher dose twice weekly for 2 weeks. Treatment with a higher dose of bortezomib repeats every 3 weeks for up to 6 courses.

Patients who are responders undergo bone marrow aspirate or biopsy and peripheral blood collection for evaluation of bone marrow cellularity, tryptase-positive mast cells, reticulin fibrosis, osteosclerosis, and angiogenesis by fluorescent in situ hybridization (FISH), immunohistochemistry, and other immunological laboratory methods.

After completion of study therapy, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Timeline

• Study Start: 2005-09
• Study First Submitted: 2007-02-15
• Study First Submitted QC: 2007-02-15
• Study First Posted: 2007-02-19
• Primary Completion: 2008-11
• Study Completion: 2008-11
• Status Verified: 2014-10
• Last Update Submitted: 2014-10-15
• Last Update Posted: 2014-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PS-341	PS-341	Designed to assess the toxicity and pilot response of PS-341 in patients with advanced myeloproliferative diseases.

Primary Outcome Measures

Name	Time	Method
Proportion of patients who show treatment success, as defined by anemia, spleen, bone marrow, or constitutional symptoms' response (complete, partial, major, or minor response)	40 weeks
Number and severity of toxicities as assessed by NCI CTCAE v3.0	40 weeks

Secondary Outcome Measures

Name	Time	Method
Effects of treatment, in terms of changes in bone marrow cellularity, tryptase-positive mast cells, reticulin fibrosis, osteosclerosis, and angiogenesis, in responding patients	40 weeks

Trial Locations

Locations (3)

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

M. D. Anderson Cancer Center at University of Texas; 🇺🇸 Houston, Texas, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States